Nuclear isolation is a common laboratory procedure which greatly facilitates the analysis of nucleotides, gene-protein interactions and other components and phenomena of cell nuclei. The principle of the method as developed in the mid-twentieth century consists of mechanical disruption of the cell membranes followed by separating the nuclei from cytoplasmic organelles and structures by sequential differential centrifugation in gradients of sucrose or other suitable media [Maggio et al., J. Cell Biol. 18 (1963) 267-291, Hymer & Kuff, J. Histochem. Cytochem, 12 (1964) 359-363]. Subsequently Blobel and Potter [Blobel & Potter, Science, 154 (1966) 1662-1665] modified the protocol of Maggio et al. [Maggio et al. 1963] with changes in the sucrose gradient density and utilization of a single 30 min centrifugation. These two protocols have been recognized and widely used as the standards for nuclear isolation. In the ensuing years, a number of variations have been employed to fit specific needs of particular tissues or nuclear components [Blobel & Potter (1966); Wray, Methods Enzymol. 40 (1975) 75-89; Bose & Allison, J. Histochem. Cytochem. 33 (1985) 65-68; Gorski et al., Cell 47 (1986) 767-776; Ho and Guenther, J. Pharmacol. Toxicol. Methods 38 (1997) 163-168; Tapalaga et al., J. Histochem. Cytochem. 50 (2002) 1599-1609, and; Prusov & Zatsepina, Biochemistry (Mosc) 67 (2002) 423-431] e.g., to preserve or remove the nuclear membranes, or adjust for the more difficult collection and disruption of cells from culture dishes or dense fibrous tissue. All the procedures introduced before the invention described herein produce samples containing nuclear outer membranes and damaged isolated nuclei. Although the method of Ho and Guenther [Ho and Guenther, (1997)] does not use high centrifugal force, it utilizes multiple homogenization steps with a rotary pestle, a 25,000×g centrifugal force step, requires the use of an ultracentrifuge rather than a table top centrifuge, takes 30 min longer total time than the methods of this invention and the isolated nuclei of Ho and Guenther are contaminated with cytoplasmic outer nuclear membrane.